Blood Reviews最新文献

PTCY has been mainly used in haploidentical transplant (haploHSCT), but its use in matched donors allowed better evaluation of infectious risk conferred separately by PTCY or donor type.

PTCY increased the risk of bacterial infections, both in haploidentical and matched donors, mainly pre-engraftment bacteremias. Bacterial infections, particularly due to multidrug-resistant Gram-negatives, were main causes of infection-related deaths.

Higher rates of CMV and other viral infections were reported, mainly in haploHSCT. The role of donor might be more important than the role of PTCY. PTCY increased the risk of BK virus associated hemorrhagic cystitis, and seemed associated with higher risk of respiratory viral infections.

Fungal infections were frequent in haploHSCT PCTY cohorts without mold active prophylaxis, but the exact role of PTCY needs to be established.

Infections appear to be increased in patients receiving PTCY, although the exact role of GvHD prophylaxis and donor type can only be assessed in prospective trials.

Core binding factor acute myeloid leukemia (CBF AML), defined by t(8;21) or inv(16), is a subset of favorable risk AML. Despite its association with a high complete remission rate after induction and relatively good prognosis overall compared with other subtypes of AML, relapse risk after induction chemotherapy remains high. Optimizing treatment planning to promote recurrence free survival and increase the likelihood of survival after relapse is imperative to improving outcomes. Recent areas of research have included evaluation of the role of gemtuzumab in induction and consolidation, the relative benefit of increased cycles of high dose cytarabine in consolidation, the utility of hypomethylating agents and kinase inhibitors, and the most appropriate timing of stem cell transplant. Surveillance with measurable residual disease testing is increasingly being utilized for monitoring disease in remission, and ongoing investigation seeks to determine how to use this tool for early identification of patients who would benefit from proceeding to transplant. In this review, we outline the current therapeutic approach from diagnosis to relapse while highlighting the active areas of investigation in each stage of treatment.

High dose Post transplant cyclophosphamide (PTCy) is now regarded as a very effective way of preventing acute and chronic GvHD, and it's use has rapidly expanded world-wide.

In search of an ideal partner or alternative to conventional immunosuppressive agents, rabbit anti-thymocyte globulin (ATG) and, more recently, post-transplant cyclophosphamide (PT-Cy) have both emerged as valid and efficient options for preventing graft-versus-host disease (GvHD). To further reduce the risk of GvHD, strategies combining ATG and PT-Cy have recently been investigated. In a haploidentical setting, retrospective studies suggest that combining PT-Cy and ATG may result in a lower incidence of chronic GvHD without increasing the risks of infection or relapse, when compared to PT-Cy without ATG. In haploidentical or unrelated donor settings, adding reduced doses of PT-Cy to ATG may reduce the risk of acute and chronic GvHD and improve survival, particularly GvHD-free, relapse-free survival (GRFS), when compared to ATG without PT-Cy. Overall, the combination of PT-Cy and ATG is a safe and promising approach for patients with hematological malignancies undergoing allogeneic hematopoietic stem cell transplantation (HSCT).

Background

Optimal peri-operative management for women with Von Willebrand disease (VWD) and heavy menstrual bleeding (HMB) remains undetermined.

Aim and methods

To evaluate (pre)operative management in relation to (post)operative bleeding after endometrial ablation (EA) and hysterectomy in VWD women with HMB by performing a database search between 1994 and 2023.

Results

Eleven cohort studies and 1 case-report were included, of overall ‘low’ quality, describing 691 operative procedures. Prophylaxis (Desmopressin, clotting factor concentrates or tranexamic acid) to prevent bleeding was described in 100% (30/30) of EA procedures and in 4% (24/661) of hysterectomies. Bleeding complications despite prophylaxis were described in 13% (3/24) of hysterectomies vs 0% (0/30) in EA.

Conclusion

VWD women often seem to experience bleeding complications during hysterectomy and all women with VWD received preprocedural hemostatic agents during EA, indicating potential under- and overdosing of current prophylactic strategies. Prospective studies are needed to determine the optimal (pre)operative strategy for gynecological surgical procedures in women with VWD.

Despite recent advancements, treatment of cytopenia due to bone marrow failures (BMF) and myeloid neoplasms remains challenging. Androgens promote renewal and maturation of blood cells and may be beneficial in these forms. Here we report a systematic review of androgens use as single agent in hematologic conditions. Forty-six studies, mainly retrospective with various androgen types and doses, were included: 12 on acquired aplastic anemia (AA), 11 on inherited BMF, 17 on myelodysplastic syndromes (MDS), and 7 on myelofibrosis. Responses ranged from 50 to 70% in inherited BMF, 40–50% in acquired AA and MDS, while very limited evidence emerged for myelofibrosis. In acquired AA, response was associated with presence of non-severe disease; in MDS androgens were more effective on thrombocytopenia or mild to moderate anemia, whilst limited benefit was observed for transfusion dependent anemia. Toxicity profile mainly consisted of virilization and liver enzyme elevation, whilst the risk of leukemic evolution remains controversial.

Close HLA matching of donors and recipients has been the dogma for successful allogeneic blood or marrow transplantation (alloBMT), to limit the complications of graft-versus-host disease (GVHD). However, many patients in need, especially those within certain ethnic groups such as those of African-Americans and Hispanics, remain unable to find a match even with the increased availability of unrelated donors. Over half a century ago, investigators at Johns Hopkins found that cyclophosphamide's immunosuppressive properties made it the ideal replacement for total body irradiation in alloBMT conditioning regimens. They also found it to be the best chemotherapeutic for preventing GVHD in animal models, but its cytotoxic properties scared them from using it clinically in the high doses successful in animal models. Subsequent work showed that cyclophosphamide spared hematopoietic and other stem cells including memory lymphocytes, prompting re-examination at high doses for GVHD prophylaxis. Animal and extensive human studies demonstrated that high-dose post-transplantation cyclophosphamide (PTCy) effectively and safely limited GVHD such that mismatched transplants are now considered standard-of-care worldwide. The beneficial effects of PTCy on GVHD appears to be independent of donor type, graft source, or conditioning regimen intensity.

Post-transplant cyclophosphamide (PTCy) allows safe and effective partially matched donor allogeneic blood or marrow transplantation (alloBMT), so that almost everyone in need of the procedure now has a donor. Moreover, PTCy and other recent advances have lowered alloBMT mortality rates to less than half of that seen before the turn of the century, at costs that are substantially less than most newly approved anticancer agents. These advances also make tailoring BMT based on patients' unique diseases and characteristics now feasible for further improving outcomes. Personalizing every aspect of alloBMT, including conditioning, donor, graft type, and post-transplant maintenance is now possible. For example, alloBMT's antitumor activity historically was restricted to the allogeneic graft-versus-tumor effect directed against histocompatibility antigens. However, replacing exhausted immune systems with healthy non-exhausted, non-tolerant ones likely can enhance the activity of novel targeted therapies. The impressive results seen with tyrosine kinase inhibitors after alloBMT for patients with both Ph+ acute lymphoblastic leukemia and FLT/ITD+ acute myeloid leukemia herald the potential of precision BMT.

Frontline therapy for multiple myeloma (MM) is evolving to include novel combinations that can achieve unprecedented deep response rates. Several treatment strategies exist, varying in induction regimen composition, use of transplant and or consolidation and maintenance. In this sea of different treatment permutations, the overarching theme is the powerful prognostic factors of disease risk and achievement of minimal residual disease (MRD) negativity. MM has significant inter-patient variability that requires treatment to be individualized. Risk-adapted and response-adapted strategies which are increasingly being explored to define the extent and duration of therapy, and eventually aim for functional curability. In addition, with T-cell redirection therapies rapidly revolutionizing myeloma treatments, the current standard of care for myeloma will change. This review analyzes the current relevant literature in upfront therapy for fit myeloma patients and provides suggestions for treatment approach while novel clinical trials are maturing.